Modulation of natural killer (NK) activity and macrophage functions have been examined. Macrophages can be activated in vitro to become suppressive and cytotoxic against tumor cells by lymphokines plus endotoxin. Other agents, such as interferon, poly I:C and exdotoxin alone, induce macrophages to become cytotoxic but not suppressive. During the early stages of macrophage activation there is an inhibition of both RNA and protein synthesis. Monoclonal antibodies against macrophage specific surface antigens have been developed. The pattern of tumor cell lysis by macrophages is similar, regardless of the source of effectors or the activating agent. However, the pattern of inhibition by various sugars differed depending on the target utilized. In addition, the pattern of inhibition of NK activity with sugars was not the same as with macrophage cytotoxicity. Macrophage circulation studies demonstrated that macrophages injected intravenously first go to the lung and then to the liver and spleen. NK activity can be suppressed in vitro by normal, nonactivated macrophages while macrophages activated by Corynebacterium parvum do not suppress. Congenic strains with high and low NK activity are being developed.